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08-09-2010 | Oncology | Article

Patient selection is biggest challenge for phase I breast cancer trials


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MedWire News: Around 20% of metastatic breast cancer patients who enter phase I clinical trials show a measurable benefit after 4 months, depending on their tumor characteristics and the biological activity of the novel agents, study results show.

The findings broadly support phase I trials for these patients, but they also "highlight many of the challenges in developing effective drugs for breast cancer," say Charles Swanton (Royal Marsden Hospital, Sutton, UK) and colleagues.

"For this process to be as cost- and time-effective as possible, phase I trial designs need to be able to adapt to rapidly evolving changes in molecular biology and the technological advances resulting from this," they add in the British Journal of Cancer.

In spite of the recent advances in drug development, most women with metastatic breast cancer have a median survival time of approximately 18-24 months, and only around 20% will be alive 5 years after the initial diagnosis of metastatic disease.

Patients who remain sufficiently well may be offered early experimental phase I trials, but appropriate advice for patients remains uncertain because of the limitations of existing literature documenting patient outcome.

In the current study, the researchers performed a retrospective review of 70 refractory metastatic breast cancer patients who participated in 30 phase I trials at the Royal Marsden Hospital between 2002 and 2009.

Median overall survival was 8.7 months and the median time-to-progression was 7.0 weeks. In all, eight (11.4%) of 70 patients obtained a partial response (PR), 12 (17.1%) had stable disease (SD), and 50 (71.4%) had progressive disease at first radiological assessment. The overall clinical benefit rate (PR+SD) at 4 months was 20%.

Patients with triple negative breast cancer had the greatest clinical benefit rate, at 30.7%, with most being treated with poly (ADP-ribose) polymerase (PARP) inhibitors or chemotherapy combinations. Meanwhile, HER2-positive patients showed a clinical benefit rate of 19% and estrogen receptor (ER)-positive/HER2-negative patients showed a rate of 8.7%.

In multivariate analysis, the factors significantly associated with overall survival were abnormal lactate dehydrogenase, a serum albumin level of ≥35 mg per 100 ml, ≥5 previous treatment lines, liver metastases, and Eastern Cooperative Group performance status ≥2 at study entry, at hazard ratios of 3.2, 0.35, 2.5, and 3.3, respectively.

Swanton and colleagues say further studies like theirs "will aid the ability to conduct successful hypothesis-testing clinical trials for targeted agents in breast cancer in molecularly distinct tumor types."

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Andrew Czyzewski

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